Categories: Vision / eye phene

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 137600 (trait) , 137750 (trait) , 138770 (trait)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal recessive

Disease-related: yes

Key variant known: no

Cross-species summary: Also known as Goniodysplasia, mesodermal and Mesodermal dysgenesis

Species-specific description: Genetics Committee of the American College of Veterinary Opthalmologists (2021): "congenital anomaly characterized by the persistence of a variably fenestrated sheet of uveal tissue spanning the iridocorneal angle, extending from the iris base to the peripheral cornea. Diagnosis is by gonioscopy, which is not part of a routine eye certification examination."

Inheritance: Pugh et al. (2019): "Analysis of pedigree information was consistent with an autosomal recessive mode of inheritance for severe goniodysgenesis (potentially leading to glaucoma) in this breed."

Mapping: A GWAS on 17 cases and 42 controls enabled Pugh et al. (2019) to map this disorder in Border Collies to a 3.8Mb region between 49,879,074 and 53,632,785 on chromosome CFA17.

Markers: Pugh et al. (2019) noted that although the association of the c.590G>A variant with goniodysgenesis in Border Collies is strong, it is not complete. Oliver et al. (2019) confirmed the incompleteness of this association in Border Collies: "Of the 90 [non-affected] controls, 71 were homozygous for the wild-type allele, two were homozygous for the [c.590G>A] variant, and 17 were heterozygous. Of the 16 cases, three were homozygous for the wild-type allele, 11 were homozygous for the variant, and two were heterozygous." In other words, the chance of this marker identifying Border Collies that are actually going to be affected is only 69% (11/16).

Molecular basis: Pugh et al. (2019) reported that analysis of "Whole genome sequences [in the candidate region] of three dogs with glaucoma, three severely affected by goniodysgenesis and three unaffected dogs identified a missense variant [c.590G>A] in the olfactomedin like 3 (OLFML3) gene in all six affected animals."

Breeds: Border Collie (Dog) (VBO_0200193), Siberian Husky (Dog) (VBO_0201233).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Associated gene: